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Concomitant use of pregabalin, opioids may increase risk for death

Coprescription of pregabalin with opioids was associated with greater odds for opioid-related death, especially at high doses, according to research published in Annals of Internal Medicine.

“Pregabalin is an anticonvulsant that is increasingly being prescribed as an adjunct for chronic pain,” Tara Gomes, MHSc, PhD, from Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, and colleagues wrote. “However, it can be sedating and may augment central nervous system depression in patients also receiving opioids.”

Gomes and colleagues performed a population-based, nested case-control study to determine if concomitant pregabalin and opioid use is associated with opioid-related mortality. The researchers enrolled individuals aged between 15 and 105 years who received public drug coverage for opioid prescriptions between Aug. 1, 1997, and Dec. 31, 2016.

A total of 1,417 participants were case patients, or those who experienced an opioid-related death that were not classified as a suicide or homicide. Case patients were matched to up to four controls (n = 5,097) based on age, sex, date of the opioid-related death, history of chronic kidney disease and Charlson comorbidity index score.

The researchers found that case patients were prescribed other central nervous system depressants, received more medications annually and had more comorbidities more often than control participants.

Adjusted analysis revealed that patients with concomitant use of pregabalin and opioids in the prior 120 days were significantly more likely to die of opioid-related causes than those only using opioids (adjusted OR = 1.68; 95% CI, 1.19-2.36). Sensitivity analyses that assessed pregabalin use overlapping the date of the opioid-related death (aOR = 1.81; 95% CI, 1.26-2.6) and matching based on prior use of central nervous system depressants (aOR = 2; 95% CI, 1.39-2.88) showed similar associations between pregabalin and opioid use and opioid-related mortality.

Patients taking a high dose of pregabalin were significantly more likely to die of opioid-related causes than those with no pregabalin exposure (aOR = 2.51; 95% CI, 1.24-5.06). Patients taking a low or moderate dose of pregabalin had lower but still significant odds of opioid-related death (aOR = 1.52; 95% CI, 1.04-2.22).

Coprescription of NSAIDs with opioids was not associated with an increased risk for opioid-related mortality (aOR = 1.04; 95% CI, 0.9-1.19).

“We found compelling evidence for a potentially life-threatening drug–drug interaction involving pregabalin and opioids similar to that previously observed with gabapentin and opioids,” Gomes and colleagues concluded.

“On the basis of these and earlier findings, we recommend caution when coprescribing gabapentinoids with opioids, particularly when the dose of either drug class is high,” they added. – by Alaina Tedesco

Disclosure: Gomes reports receiving grants from Ontario Ministry of Health and Long-Term Care. Please see study for all other authors’ relevant financial disclosures.